Negative-sense RNA

Negative-sense RNA is RNA whose sequence is complementary to the corresponding messenger RNA sequence. “Negative” specifies orientation relative to a coding message; it does not mean negative electric charge, damage, or lack of biological function. A negative-sense viral genome must first be copied into a message-compatible Positive-sense RNA before its encoded proteins can be made by translation.

For a short illustrative message $5^{\prime }\text{-AUGGCU-}{3}^{\prime }$, the complementary template is $3^{\prime }\text{-UACCGA-}{5}^{\prime }$, equivalently $5^{\prime }\text{-AGCCAU-}{3}^{\prime }$ when written in the conventional direction. The strands are complementary and antiparallel. Simply reversing the letters, without exchanging complementary bases, would not produce the negative-sense template. This small example shows why both sequence and direction matter.

The requirement creates a startup problem for a virus: if the entering genome cannot itself serve as messenger RNA, how can it make the enzyme needed to copy that genome? Vesicular stomatitis virus solves this by carrying an RNA-dependent RNA polymerase in its viral particle. In the 1970 experiment by D. Baltimore, A. S. Huang and M. Stampfer, virion preparations incorporated supplied ribonucleotide substrates into new RNA; the main product was complementary in sequence to the viral genome.^[ref]

This experiment connects a sequence classification to physical machinery packaged with the genome. Positive-sense RNA and Negative-sense RNA describe the relation of an RNA region to the coding message; identifying the sense does not by itself specify all details of genome segmentation, replication intermediates or transcription control.